Cocaine continues to be a widely abused psychostimulant drug, yet no consistent treatment for cocaine addiction exists. One roadblock in the development of pharmacological treatments for drug addiction has been an incomplete understanding of the neuroadaptations that occur during the development of addiction. The transition in human cocaine users from a state of casual, occasional cocaine use to a state of addiction, including consistent drug-taking, has not been well characterized in animal models of drug use. Thus, we aim to identify the protein expression changes that occur during the acquisition of cocaine self-administration (SA) behavior in rats as a model of the neuroadaptations that occur in humans during the developmental history of addiction. We hypothesize that the neuroadaptations that occur during the acquisition of cocaine SA will differ from those that occur over the same time period of response-independent cocaine infusions or SA of a sucrose reinforcer. We will use two-dimensional gel electrophoresis to identify and microinfusion of inhibitors to manipulate the protein expression changes that correlate with the development of consistent drug-taking.